The objective of this project is to identify by functional and genetic analysis the cellular factors necessary for the transformation of specific cell types by avian RNA tumor viruses, and factors which contribute to the malignant phenotype in vivo. For these studies cells of defined embryonic origin and expressing or capable of expressing defined macromolecular products which serve as cell-type markers will be employed. The ability of avian RNA tumor viruses to infect and transform both target and non-target cells will be examined for differences in virus-cell interactions, virus replication, virus expression and effect of the transformation gene on the cell's type-specific program. In vitro differentiation systems utilizing limb bud cultures infected by Rous sarcoma virus and yolk sac cultures infected by avian myeloblastosis virus will be examined. A more detailed study on the mechanism of suppression of cell-type specific macromolecular synthesis in myoblasts and chondroblasts infected with temperature-sensitive mutants of Rous sarcoma virus will be pursued at the molecular and cellular levels. The possible interaction of src with cytoskeletal elements is being explored. In vivo experiments will be performed using ts-RSV transformed Fisher Rat Liver (FRL) cells. Cell phenotype will be examined following successive in vivo passages.